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Licensed Unlicensed Requires Authentication Published by De Gruyter October 10, 2007

Measurement of arginine derivatives in pediatric patients with chronic kidney disease using high-performance liquid chromatography-tandem mass spectrometry

Sihe Wang, Faye B. Vicente, Alan Miller, Ellen R. Brooks, Heather E. Price and Frederick A. Smith
From the journal


Background: The arginine derivatives asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) interfere with endothelial nitric oxide synthesis. Plasma ADMA and SDMA have been shown to be risk factors for cardiovascular disease and/or kidney function deterioration in a variety of patient populations.

Methods: We developed a method to quantitatively measure arginine, ADMA, and SDMA using HPLC-tandem mass spectrometry. 13C6-L-Arginine was used as the internal standard, while the derivatives were separated on a silica column in less than 14 min. Plasma levels of ADMA, SDMA, and arginine were measured in children with stage II or III chronic kidney disease (CKD) and age- and gender-matched siblings.

Results: The chromatography exhibited no observable ion suppression in the patient specimens tested. There was no apparent carryover for any of the analytes. The assay was linear over 0.32–2.29, 0.23–4.43, and 1.00–303.89 μmol/L for ADMA, SDMA, and arginine, respectively. Plasma ADMA, SDMA, and arginine (mean±SD) were 1.10±0.35, 2.06±1.11, and 57.93±22.10 μmol/L for children with CKD, and 0.78±0.16, 0.71±0.23, and 65.29±21.30 μmol/L for the healthy siblings.

Conclusions: The method exhibited no observable ion suppression in the patient specimens tested and has an acceptably short analytical cycle time. Children with CKD had higher levels of ADMA and SDMA than the healthy siblings.

Clin Chem Lab Med 2007;45:1305–12.

Corresponding author: Sihe Wang, Department of Clinical Pathology, The Cleveland Clinic, 9500 Euclid Avenue L11, Cleveland, OH 44195, USA Phone: +1-216-4452634, Fax: +1-216-4444414,

Received: 2007-3-8
Accepted: 2007-5-24
Published Online: 2007-10-10
Published in Print: 2007-10-01

©2007 by Walter de Gruyter Berlin New York